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Scientific article
English

Physicochemical Profiling of Sartans: Detailed Study of Ionisation Constants and Distribution Coefficients

Contributors

Tosco, Paolo; Rolando, Barbara; Fruttero, Roberta; Henchoz, Yveline; Martel, Sophie; Carrupt, Pierre-Alain; Gasco, Alberto

Published in

Helvetica chimica acta, vol. 91, p. 468-482

Publication date

2008

Abstract

A detailed investigation of the ionization and lipophilicity profiles of selected sartans (valsartan, losartan, irbesartan, candesartan, candesartan cilexetil), a class of antihypertensives commonly used in therapy, is presented. The pKa macroconstants were determined by integrated potentiometry, capillary electrophoresis, and UV spectrophotometry. The measured pKa macroconstants were connected with the ionizable centers present in each molecule with the aid of model compounds. Potentiometric titrations with the GLpKa apparatus were performed to determine the distribution profile (logD vs. pH) of valsartan, while the shake-flask procedure was used to characterize the distribution profile of the other compounds. Valsartan showed a lipophilicity profile consistent with the presence of two acidic centers. Losartan and irbesartan, which contain one acidic and one basic center, displayed the classical bellshaped profile of ordinary ampholytes. By contrast, a more complex situation emerged in the case of candesartan, due to the large number of ionization equilibria involved. The low solubility of candesartan cilexetil, together with the ease of hydrolysis of the ester moiety, prevented a successful investigation of its ionization and lipophilicity profiles.

UNIGE affiliation entities

Citation (ISO format)

TOSCO, Paolo et al. Physicochemical Profiling of Sartans: Detailed Study of Ionisation Constants and Distribution Coefficients. In: Helvetica chimica acta, 2008, vol. 91, p. 468–482. doi: 10.1002/hlca.200890051

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Article (Published version)

Identifiers

Journal ISSN

0018-019X
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Technical informations

Creation

06/11/2009 11:47:00

First validation

06/11/2009 11:47:00

Update

14/03/2023 15:17:19

Status update

14/03/2023 15:17:18

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